Targeted therapy

Targeted therapy is a type of medicationwhich blocks the growth of cancer cellsby interfering with specific targeted moleculesneeded for carcinogenesisand tumorgrowth, rather than by simply interfering with rapidly dividing cells. Targeted cancer therapies may be more effective than current treatments and less harmful to normal cells.

The main categories of targeted therapy are small molecules and monoclonal antibodies.

Small molecules

Image:Mechanism imatinib.jpg

• Imatinib mesylate(Gleevec®, also known as STI?571) is approved for chronic myelogenous leukemia, gastrointestinal stromal tumorand some other types of cancer. Early clinical trials indicate that imatinib may be effective in treatment of dermatofibrosarcoma protuberans.
• Gefitinib(Iressa®, also known as ZD1839), targets the epidermal growth factor receptor(EGFR) tyrosine kinaseand is approved in the U.S.for non small cell lung cancer. EGFR is also overexpressed in the cells of other solid tumors, such as lung and breast cancers. This leads to inappropriate activation of the apoptoticRassignal transductioncascade, eventually leading to uncontrolled cell proliferation.Gefitinib inhibits EGFR tyrosine kinase by binding to the adenosine triphosphate(ATP)-binding site of the enzyme. Thus the function of the EGFR tyrosine kinase in activating the Ras signal transduction cascade is inhibited; and malignant cells are inhibited.
• Erlotinib(marketed as Tarceva). Erlotinib works through a similar mechanism as gefitinib. Erlotinib has been shown to increase survival in metastatic non small cell lung cancerwhen used as second line therapy. Because of this finding, erlotinib has replaced gefitinib in this setting.
• Bortezomib(Velcade®) is an apoptosis-inducing drug that causes cancer cells to undergo cell death by interfering with proteins. It is approved in the U.S.to treat multiple myelomathat has not responded to other treatments.

Monoclonal antibodies

Main article: Monoclonal antibody

Examples of monoclonal antibodies include:

• Rituximabtargets CD20 found on B cells. It is used in non Hodgkin lymphoma
• Trastuzumab(Herceptin®) targets the Her2/neu(also known as ErbB2) receptor expressed in some types of breast cancer
• Cetuximab(marketed as Erbitux) targets the epidermal growth factor receptor. It is used in the treatment of colon cancer.

Progress and future

Many oncologists believe that targeted therapies are the chemotherapy of the future. As solid tumor cancer continues to be viewed as a chroniccondition, methods for long-term treatment, with less side-effects, continue to be investigated.

In the U.S., the National Cancer Institute's Molecular Targets Development Program (MTDP) to identify and evaluate molecular targets that may be candidates for drug development.

References

• Green, Mark Targeting Targeted TherapyNew England Journal of Medicine (May 20, 2004)
• Molecular Oncology: Receptor-Based TherapyJournal of Clinical Oncology (April 10, 2005)
• Lynch, Thomas Activating Mutations in the Epidermal Growth Factor Receptor Underlying Responsiveness of Non?Small-Cell Lung Cancer to GefitinibNew England Journal of Medicine (May 20, 2004)

See also

• Advances in Targeted Cancer Therapies
• National Cancer Institute Fact Sheet

This article is licensed under the GNU Free Documentation License.
It uses material from the http://en.wikipedia.org/wiki/Targeted+therapy Wikipedia article Targeted therapy.